氰化钠加重缺氧诱导的小鼠脑神经损伤及机制  

Sodium cyanide exacerbates hypoxia induced brain nerve damage in mice and its mechanism

作　　者：李鹏飞 石华香 周梦玮 郭家彬 王永安 王丽韫 LI Pengfei;SHI Huaxiang;ZHOU Mengwei;GUO Jiabin;WANG Yongan;WANG Liyun(State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Toxicology and Phar-macology,Academy of Military Medicine Sciences,Beijing 100850,China;Center for Disease Control and Prevention of PLA,Beijing 100071,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850 [2]中国人民解放军疾病预防控制中心,北京100071

出　　处：《中国药理学与毒理学杂志》2024年第2期89-96,共8页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的研究氰化钠(NaCN)急性染毒对密闭缺氧致小鼠脑神经损伤的作用及机制。方法①将小鼠随机分为缺氧+NaCN〔0(缺氧对照组),2.56,3.8和5.1 mg·kg^(-1)〕组,ip给予不同浓度NaCN染毒后立即放入密闭缺氧罐,观察小鼠缺氧存活时间。②将小鼠分为正常对照组、NaCN 3.8 mg·kg^(-1)组、缺氧30和60 min组及NaCN(3.8 mg·kg^(-1))+缺氧(30和60 min)组,按分组处理后,用动脉血气分析仪检测小鼠动脉血气指标酸碱度(pH)、氧饱和度(sO_(2))、氧分压(pO_(2))和二氧化碳分压(pCO_(2));用激光散斑成像仪检测小鼠大脑皮质脑血流;分别称量脑组织干、湿重,计算脑组织含水率;试剂盒检测海马总超氧化物歧化酶(T-SOD)活性和丙二醛(MDA)含量;TUNEL染色检测小鼠海马细胞凋亡率;HE染色检测海马组织病理变化。结果①与缺氧对照组比较,缺氧+NaCN各剂量组小鼠缺氧存活时间均显著延长(P<0.01)。②与正常对照组相比,缺氧30 min组动脉血pCO_(2)上调(P<0.05),pH和pO_(2)下调(P<0.05);缺氧60 min组pCO_(2)上调(P<0.05),皮质脑血流下调(P<0.01);NaCN 3.8 mg·kg^(-1)组动脉血pO_(2)和sO_(2)显著下调(P<0.05),皮质脑血流显著下调(P<0.01),MDA含量和T-SOD活性显著上调(P<0.01),脑组织含水率增加(P<0.01)。与缺氧30 min组相比,NaCN+缺氧30 min组sO_(2)和pO_(2)显著上调(P<0.05),pCO_(2)显著下调(P<0.05);分别与缺氧30或60 min组比较,NaCN+相应时间缺氧组皮质脑血流均显著下调(P<0.01),MDA含量、T-SOD活性和脑组织含水率显著上调(P<0.01)。HE染色结果显示,NaCN 3.8 mg·kg^(-1)组、NaCN+缺氧30或60 min组海马细胞出现明显的细胞肿胀和空泡化,神经元数量减少,出现核固缩和核深染,缺氧30和60 min组海马细胞未见明显改变。TUNEL染色结果显示,NaCN 3.8 mg·kg^(-1)组与正常对照组比较、NaCN+缺氧30 min组与缺氧30 min组比较、NaCN+缺氧60 min组与缺氧60 min组比较,小鼠海马细胞凋亡率均显著增加(P<0.05)。结�OBJECTIVE To investigate the effect and mechanism of acute exposure to sodium cyanide(NaCN)on brain nerve damage induced by closed hypoxia in mice.METHODS①Mice were randomly divided into hypoxia+NaCN 0(hypoxia control group),2.56,3.8,and 5.1 mg·kg^(-1)groups.After ip adminis⁃tration of different concentrations of NaCN,the mice were immediately placed into a closed hypoxic tank and the hypoxia survival time was observed.②Mice were divided into normal control,NaCN 3.8 mg·kg^(-1),hypoxia(30 and 60 min)and NaCN 3.8 mg·kg^(-1)+hypoxia(30 and 60 min)groups.After grouping,the pH,oxygen saturation(sO_(2)),oxygen tension(pO_(2))and carbon dioxide partial pressure(pCO_(2))of arterial blood of mice were detected using an arterial blood gas analyzer.The cortical cerebral blood flow of mice was detected using a laser speckle imager.The dry and wet brain tissue were weighed separately,and the brain moisture content was calculated.The kit was used to detect the activity of total superoxide dismutase(T-SOD)and the content of malondialdehyde(MDA)in the hippocampus.TUNEL staining was used to detect the apoptosis rate of cells in the hippocampus.HE staining was used to detect path⁃ological changes in the hippocampus.RESULTS①Compared with the hypoxic control group,the sur⁃vival time of mice in the hypoxic+NaCN groups was significantly prolonged(P<0.01).②Compared with the normal control group,the hypoxia 30 min group showed upregulation of arterial blood pCO_(2)(P<0.05),downregulation of pO_(2)(P<0.05).The hypoxia 60 min group showed upregulation of arterial blood pCO_(2)(P<0.05)and downregulation of cortical cerebral blood flow(P<0.05).In the NaCN 3.8 mg·kg^(-1)group,arterial blood pO_(2)and sO_(2)were significantly downregulated(P<0.05),so was cortical cerebral blood flow(P<0.01),but MDA content and T-SOD activity were significantly upregulated(P<0.01),and the brain moisture content was increased(P<0.01).Compared with the hypoxia 30 min group,sO_(2)and pO_(2)of arterial blood in the NaCN+hypoxia 30 min group were

关 键 词：氰化钠 缺氧 海马 动脉血气 脑血流 

分 类 号：R12[医药卫生—环境卫生学] R959[医药卫生—公共卫生与预防医学]